We propose to study in mice the mechanism of neurodegeneration caused by paralytogenic ecotropic wild mouse type C virus. Our approach to this long-term goal includes (1) determination of mode of replication of the neurotropic type C virus in the central nervous system of mice, (2) determination of viral gene expression, both at the transcriptional and translational levels in isolated neurons of paralyzed and nonparalyzed viremic mice and, (3) examination of the role of subvirion components in membrane damage or alteration and degeneration of neurons. The major analytical techniques which will be used in this investigation are DNA-DNA and DNA-RNA hybridization, radioimmunoassay, membrane receptor binding assay, large-scale preparation of virus and purification of subvirion components, immunofluorescent and immunoperoxidase staining, etc. It is expected that this investigation of the paralytogenic ecotropic wild mouse virus replication and gene expression in neurons of mice at various stages of the experimental transmission of the paralytic disease, together with the studies on possible neurotoxic effects of subvirion components, will provide basic information on the mechanism of neuronal degeneration in experimental mice. Since amyotrophic lateral sclerosis and other human motor neuron diseases (spongiform encephalopathies) share several prominent features with the wild mouse type C virus-induced paralytic disease, we hope that this study will provide insight into the possible mechanism of neurodegeneration in similar diseases of animals and man.